An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

• Type of Material: Article
• Authors: Ahmed O Hassan, Washington University in St. Louis; Swathi Shrihari, Washington University in St. Louis; Matthew J Gorman, Massachusetts Institute of Technology; Baoling Ying, Washington University in St. Louis; Dansu Yaun, Massachusetts Institute of Technology; Saravanan Raju, Washington University in St. Louis; Rita E Chen, Washington University in St. Louis; Igor P Dmitriev, Washington University in St. Louis; Elena Kashentseva, Washington University in St. Louis; Lucas J Adams, Washington University in St. Louis; Colin Mann, La Jolla Institute for Immunology; Mehul E Davis-Gardner, Emory University; Mehul Suthar, Emory University; Pei-Yong Shi, University of Texas Medical Branch, Galveston; Erica Ollmann Saphire, La Jolla Institute for Immunology; Daved H Fremont, Washington University in St. Louis; David T Curiel, Washington University in St. Louis; Galit Alter, Massachusetts Institute of Technology; Michael S Diamond, Washington University in St. Louis
• Language: English
• Date: 2021-07-27
• Publisher: CELL PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Author(s)
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2021.109452
• Title of Journal or Parent Work: CELL REPORTS
• Volume: 36
• Issue: 4
• Start Page: 109452
• End Page: 109452
• Grant/Funding Information: This study was supported by NIH contracts and grants (R01 AI157155, R01 EB026468-02S1, 75N93019C00062, 75N93021C00017, HHSN272201400018C, and U19 142790) and INV-00613 from the Bill and Melinda Gates Foundation.; This work also was supported by Woodruff Health Sciences Center 2020 COVID-19 CURE Award.
• Keywords: Life Sciences & Biomedicine; Science & Technology; ACE2; Cell Biology; MOUSE; NEUTRALIZING ANTIBODIES
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology; Health Sciences, Immunology

Abstract

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.